Chromosome structure abnormalities can be either unbalanced rearrangements or balanced rearrangements. The various kinds of unbalanced rearrangements are detailed below. Unbalanced rearrangements involve deletion, duplication or both. Deletion of a chromosome segment leads to partial monosomy of that segment. Duplication of a chromosome segments leads to partial trisomy of that segment. Any mutation leading to an imbalance like monosomy, trisomy or other can result in an abnormal phenotype.
A deletion is loss of a chromosome segment. There are two kinds of deletions: terminal, at the end of a chromosome; and interstitial, along a chromosome arm. Deletions can occur if a chromosome simply breaks and part of it floats away. Also, deletions can occur of misaligned chromatids cross over unequally. In addition, deletions can occur if balanced translocations or inversions segregate abnormally.
A carrier individual -- with one chromosome carrying the deletion, and another chromosome lacking the deletion -- is monosomic for the affected genes. Monosomy usually leads to haploinsufficiency, which arises when two copies of a gene are necessary and only one copy is insufficient. Monosomy of a hormone-encoding gene is usually haploinsufficient, since one gene copy cannot encode for enough production of that hormone.
|Duplications||Duplications, like deletions, can arise by unequal crossing over or abnormal segregation. Phenotypic abnormalities can arise if the duplication results in an extra gene copy (partial trisomy), leading to over-expression. Also, duplications within a gene can destroy its function, thus leading to haploinsufficiency.|
|Markers & Rings|
Marker chromosomes (aka supernumary chromosomes or extra structurally abnormal chromosomes) are very small and unnamed chromosomes which usually exist in addition to a normal diploid. Marker chromosomes usually consist of just centromeric heterochromatin. Larger marker chromosomes, though, contain some material from one or both chromosome arms; this disruption can lead to phenotypic abnormalities. Neocentromeres are marker chromosomes stable during mitosis which lack centromeric DNA, but which somehow have centromere activity.
When a chromosome undergoes two breaks, chromosomal DNA can separate and form a ring structure. This form of marker is known as a ring chromosome. Although quite rare, ring chromosomes containing centromeric DNA are mitotically stable. However, sometime sister ring chromatids can tangle while trying to separate during anaphase. This tangling can lead to breakage, resulting in demise of the ring chromosome or even causing new ring chromosomes to form of unequal size. Thus, ring chromosomes are rarely found in all of an organism's cells.
High-resolution banding is ineffective at detecting marker chromosomes because most makers are too small to even discern the bands. However, FISH using probes for centromeric heterochromatin can usually visualize marker chromosomes.
|Isochromosomes||Isochromosomes arise when one arm of a chromosome goes missing, and the remaining arm is duplicated to form a mirror image. In a diploid cell, this leads to partial trisomy of the genetic material from one arm (the duplicate arms, and arm on the homologous chromosome) and partial monosomy of the genetic material from the other arm.|
|Dicentrics||Although very rare, a dicentric occurs when centromere-containing fragments fuse together to form a new chromosome with two centromeres. Dicentrics can be mitotically stable if one centromere is inactivated, or if the chromosome is pseudodicentric. A pseuodicentric chromosome has centromeres which move to only one pole or the other during anaphase.|
High-resolution banding can detect deletions and duplications on the magnitude of several thousand base-pairs, and FISH can detect very small or uncertain deletions.